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Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression

Published online by Cambridge University Press:  22 November 2017

Patrícia P. Silveira*
McGill University Canadian Institute for Advanced Research
Irina Pokhvisneva
McGill University
Carine Parent
McGill University
Shirong Cai
Singapore Institute for Clinical Sciences Agency for Science, Technology and Research (A*STAR)
Anu Sathyan Sathyapalan Rema
Singapore Institute for Clinical Sciences Agency for Science, Technology and Research (A*STAR)
Birit F. P. Broekman
Singapore Institute for Clinical Sciences Agency for Science, Technology and Research (A*STAR)
Anne Rifkin-Graboi
Singapore Institute for Clinical Sciences Agency for Science, Technology and Research (A*STAR)
Michael Pluess
Queen Mary University of London
Kieran J. O'Donnell
McGill University Canadian Institute for Advanced Research
Michael J. Meaney
McGill University Canadian Institute for Advanced Research Singapore Institute for Clinical Sciences Agency for Science, Technology and Research (A*STAR)
Address correspondence and reprint requests to: Patrícia Pelufo Silveira, Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Douglas Mental Health University Institute, Montreal, Québec, H4H 1R3, Canada; E-mail:


While many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.

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This work was funded by the Toxic Stress Research network of the JPB Foundation. The Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) Cohort was funded by the Canadian Institutes for Health Research, the Ludmer Family Foundation, the Norlien Foundation (Calgary, Canada), the WOCO Foundation (London, Canada), the Blema & Arnold Steinberg Family Foundation, and the Faculty of Medicine of McGill University. Additional funding was provided by the Jacobs Foundation (Switzerland). The Growing Up in Singapore Towards Healthy Outcomes (GUSTO) project is funded by the National Medical Research Council (Singapore) and the Agency for Science, Technology and Research (Singapore). We thank the MAVAN and GUSTO study groups and all staff. The voluntary participation of all families is greatly appreciated.


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Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression
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Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression
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Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression
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